No significant safety signals seen with three-dose vaccine

Action Points

Note that this randomized trial of a novel, heat-stable rotavirus vaccine proved efficacy in preventing the disease in sub-Saharan Africa.

Mortality rates from rotavirus infection are highest in that part of the world.

An oral vaccine against rotavirus protected healthy infants in Africa against the disease better than placebo, results from a phase III trial showed.

In both per-protocol and intention-to-treat (ITT) analyses, vaccine efficacy of three doses of BRV-PV, a heat-stable, live, oral bovine rotavirus pentavalent vaccine, in the intervention group was 66.7% (95% CI 49.9-79.9) and 69.1% (95% CI 55.0-78.7) respectively, reported Sheila Isanaka, ScD, of Epicentre, in Paris, and colleagues.

Epicentre is a non-profit organization created by doctors from Médicins san Frontières.

There also were no significant safety concerns observed with the vaccine, with the rate of serious adverse events slightly lower in the intervention group compared with the placebo group (8.3% versus 9.1%), the authors wrote in the New England Journal of Medicine.

BRV-PV was developed by the Serum Institute of India as an alternative to the two live, oral attenuated vaccines against rotavirus (Rotarix and RotaTeq), the authors explained. They noted that rotavirus is especially challenging in sub-Saharan Africa, which has has the highest rate of death linked to the disease, and that current supply and storage capabilities make refrigeration of the vaccine difficult.

An accompanying editorial by Mathruam Santosham, MD, of Johns Hopkins University in Baltimore, and Duncan Steele, PhD, of the Bill and Melinda Gates Foundation in Seattle, stated that having vaccines available from several manufacturers will help to increase global supply.

"Despite this modest efficacy [of BRV-PV], the absolute public health benefits of vaccination are large, given the tremendous disease burden," they wrote. "Increased availability of low-cost, programatically suitable vaccines in abundant supply will be key to achieving this goal."

Isanaka 's group conducted a randomized, double-blind, placebo-controlled, event-driven trial in the African country of Niger. The ITT analysis was comprised of 4,092 infants, who underwent randomization, and received at least one dose of the vaccine. Of those, 1,780 infants in the vaccine group and 1,728 infants in the placebo group received either the complete three-dose series or placebo at 6, 10, and 14 weeks of age.

Overall, there were 31 cases of severe rotavirus gastroenteritis (a score of ≥11 on the 20-point Vesikari clinical scoring system) beginning 28 days after dose three in the vaccine group compared with 87 in the placebo group (2.14 cases versus 6.44 cases per 100 person-years). The authors estimated the vaccine prevented 4.30 (95% CI 2.75-5.85) episodes of severe rotavirus gastroenteritis per 100 person-years.

"[Other] considerations have included the epidemiologic features of rotavirus infection ... (e.g., earlier age at first infection among children in Africa) ... host characteristics (e.g., poor nutritional status and differences in the gut microbiome) ... and interference from maternal antibodies in breast milk," the authors wrote.

Examining adverse events, they found no significant between group differences in risk, with a slightly higher portion of the vaccine group reporting adverse events compared with the control group (68.7% versus 67.2%).

There was also no significant difference in the number of deaths (27 deaths in the vaccine group versus 22 in the placebo group). The authors noted that the most common causes of death were infections and infestations (37 infants). While there were no confirmed cases of intussusception, the authors said that the study was "not powered to detect an increase of rare events."

Study limitations included that BRV-PV was not consistently given concomitantly with the oral polio vaccine, and that the Vesikari score may have been underestimated, as it is designed for settings with high parental literacy.

The authors noted that 33 countries in sub-Saharan Africa are either using or plan to introduce rotavirus vaccines, and "BRV-PV does not require refrigeration and has reasonably efficacy with respect to morbidity and mortality." They added that while there were no safety concerns with this trial, "larger scale-surveillance" may be needed in order to establish safety.

This study was supported by Médicins san Frontières Operational Center in Geneva and the Kavli Foundation.

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